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Breast cancer grows in stiff tissue, but simple body stretching can reduce tumor size by more than 50%

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Stiffer breast tissue creates an environment more prone to cancer by enabling the disease to interfere with the surrounding healthy cells, according to a recent study published in Biomaterials.

Scientists studying tumor growth and metastasis at the University of Notre Dame fabricated a human tissue model to examine how cancer cells interact with connective tissue in the breast. The model allowed the team to control the stiffness of the tissue, mimicking both healthy and cancerous breast tissue structures. They found manipulation of fat cells to be stiffness-dependent.

“One of the interesting things we’re looking at is how cancer interacts with surrounding cells and how it manipulates those cells to its own benefit,” said Pinar Zorlutuna, assistant professor in the Department of Aerospace and Mechanical Engineering and the Harper Cancer Research Institute at the University of Notre Dame. “The goal of these tissue engineered cancer models is to mimic the physiological environment of the tumor, so we can use them as a platform to study breast cancer in the human tissue microenvironment.”

Fat cells, collagen fibers and epithelial cells make up the microenvironment of breast tissue. Cancer typically appears around the epithelial cells. Previous studies looking at differences between healthy and cancerous tissue found that the cancerous tissue differed in stiffness. According to Zorlutuna’s study, stiff tissue can present a microenvironment susceptible to tumor growth by enabling the cancer cells to modulate its surrounding connective tissue cells.

“If you have a stiffer environment, the cancer cell can do more manipulation of its immediate microenvironment,” Zorlutuna said. “The model allowed us to study varying levels of stiffness in the tissue. In tissue with normal stiffness, the cancer cells did not interfere with the state of the surrounding stromal cells. In tests where the tissue was stiffer, the cancer halted the differentiation process of the surrounding fat stem cells, favoring a more stem cell-like state creating a microenvironment that favors a tumor to grow.”

Researchers have typically conducted similar studies using animal models. While these tests can help advance an understanding of the disease, Zorlutuna said they could also pose a challenge.

“Animals and humans are quite different,” she said. “If you’re looking at tissue environment, mobility and the immune system, mouse models, for example, are as different to human models as the pancreas is to the lung.”

Those models can also pose a challenge to drug discovery. A fraction of the drugs proven effective in mice actually makes it through clinical trials when tested on humans, Zorlutuna said. The results of this study could help make the case for tissue engineered human disease models to be used as part of a parallel approach to drug screening before administering those drugs in clinical trials.

A team of researchers based out of Harvard Medical School, the Dana Farber Cancer Institute, and the University of Vermont has found that stretching reduces tumor growth by 52 percent in mice injected with breast cancer cells. The team's study is published in the journal Scientific Reports.

Sixty-six female mice were injected with tumors then randomized to two groups. Mice in the first group received ten minutes of stretching once a day for four weeks, in which they were "held by the tail and gently lifted, allowing the front paws to grasp a bar" (see figure A below)." Mice in the second group were simply placed on a table for the ten minutes.

After four weeks, tumors in the stretched mice were half the size of those in control group mice on average (see figure B above), an impressive result. Examining the tumors and the surrounding cells after the study period, the researchers found signs of reduced inflammation and boosted immune cell activity in the stretched mice.

Northwestern University medical researcher Dr. Sam Weinberg expressed skepticism at the study's large effect size, but says the findings are definitely worth exploring further.

"I suspect that any micro injury may improve tumor clearance if the immune system gets active," he said.

Weinberg would love to see a follow-up study on a mouse model with non-injected breast tumors where the researchers observe if stretched mice actually live longer than unstretched controls. He expressed concern that stretching could actually cause the tumors to break up and spread, a worry that the researchers shared in their paper as well.

The researchers say their study is the first report of reduced cancer growth in response to stretching. Make no mistake, however, it does not indicate stretching as a primary treatment for cancer. Further research will be needed to verify the impressive early results and ascertain any negative side effects. After more successful animal trials, human studies could follow.

Resistance exercise has already been linked to a lower risk of death in cancer patients, so it's possible stretching could have similar benefits.

"The potential clinical significance of our results lies in the possibility of developing a method of gentle stretching that could be well tolerated and testable in humans for primary or secondary cancer prevention, or in conjunction with cancer treatment," the researchers write.


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